Ann Surg Treat Res.  2019 Jul;97(1):27-35. 10.4174/astr.2019.97.1.27.

Urinary transglutaminase 2 as a potent biomarker to predict interstitial fibrosis and tubular atrophy of kidney allograft during early posttransplant period in deceased donor kidney transplantation

Affiliations
  • 1Division of Kidney and Pancreas Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. sshin@amc.seoul.kr
  • 2Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 3Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, Seoul, Korea.

Abstract

PURPOSE
Transglutaminase type 2 (TG2) is an extracellular matrix crosslinking enzyme with a pivotal role in kidney fibrosis. We tested whether quantification of urinary TG2 may represent a noninvasive method to estimate the severity of kidney allograft fibrosis.
METHODS
We prospectively collected urine specimens from 18 deceased donor kidney transplant recipients at 1-day, 7-day, 1-month, 3-month, and 6-month posttransplant. In addition, kidney allograft tissue specimens at 0-day and 6-month posttransplant were sampled to analyze the correlation of urinary TG2 and kidney allograft fibrosis.
RESULTS
Thirteen recipients had increased interstitial fibrosis and tubular atrophy (IFTA) scores at the 6-month protocol biopsy (IFTA group). The mean level of urinary TG2 in the IFTA group was higher compared to that of 5 other recipients without IFTA (no IFTA group). Conversely, the mean level of urinary syndecan-4 in the IFTA group was lower than levels in patients without IFTA. In the IFTA group, double immunofluorescent staining revealed that TG2 intensity was significantly upregulated and colocalizations of TG2/heparin sulfate proteoglycan and nuclear syndecan-4 were prominent, usually around tubular structures.
CONCLUSION
Urinary TG2 in early posttransplant periods is a potent biomarker for kidney allograft inflammation or fibrosis.

Keyword

Biomarkers; Transglutaminase 2; Kidney transplantation

MeSH Terms

Allografts*
Atrophy*
Biomarkers
Biopsy
Extracellular Matrix
Fibrosis*
Humans
Inflammation
Kidney Transplantation*
Kidney*
Methods
Prospective Studies
Proteoglycans
Syndecan-4
Tissue Donors*
Transplant Recipients
Biomarkers
Proteoglycans
Syndecan-4

Figure

  • Fig. 1 Urinary biomarkers after adjusted for creatinine (mg/mL) normalization in the interstitial fibrosis and tubular atrophy (IFTA) and no IFTA groups. (A) The level of urinary transglutaminase 2 (TG2) (ng/mL) in the IFTA group was significantly increased compared with the no IFTA group at 3- and 6-month posttransplant follow-up periods. (B–D) The level of urinary syndecan-4 (SDC4) (pg/mL), α-1 microglobulin (A1M) (ng/mL), and IL-6 (fg/mL) between the 2 groups showed no significant differences. Cr, creatinine.

  • Fig. 2 Double immunofluorescence staining and confocal microscopy in representative allograft biopsy specimens in the interstitial fibrosis and tubular atrophy (IFTA) and no IFTA groups. (A) Transglutaminase 2 (TG2) intensity was significantly upregulated at the 6-month posttransplantation biopsies compared to those at 0-day posttransplantation. (B) TG2 intensity upregulation was prominent especially in tubular structures. (C) Colocalization of syndecan-4 and the nucleus was seen in biopsy specimens. HSPG, heparin sulfate proteoglycan.

  • Fig. 3 (A, B) Intensity of transglutaminase 2 (TG2) and syndecan-4 (SDC4) in 0-day and 6-month biopsy specimens in the interstitial fibrosis and tubular atrophy (IFTA) and no IFTA groups in kidney structures. (C, D) Confocal microscopy intensity of TG2/heparan sulfate proteoglycan (HSPG) and SDC4/nuclear colocalization.


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